Species difference in N-hydroxylation of a tryptophan pyrolysis product in relation to mutagenic activation.
Metabolic activation of a tryptophan pyrolysate, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in liver microsomes from rats, mice, hamsters, guinea pigs, and rabbits was studied to know whether N-hydroxylation is a common obligatory step for mutagenic activation of Trp-P-2. Among hepatic microsomes obtained from untreated animals, the highest activity of Trp-P-2 N-hydroxylase was observed in microsomes from hamsters, followed by those from guinea pigs, mice, and rabbits. In rats, the activity was low, and there was no appreciable difference between the sexes. The activity of Trp-P-2 N-hydroxylase in microsomes was increased by pretreating the animals with a polychlorinated biphenyl mixture. The induction was most profound in rats, and the activity was enhanced 257-fold, as compared to that of untreated animals. The activity was also enhanced in microsomes from polychlorinated biphenyl mixture-treated rabbits, mice, and hamsters, while the activity was increased only slightly in guinea pigs and was thereby lowest among microsomes from the polychlorinated biphenyl mixture-treated animals. In bacterial mutagenesis test systems using Salmonella typhimurium TA 98, the number of revertants induced by Trp-P-2 was increased in parallel with the microsomal ability of the N-hydroxylation. These results indicate that in all species examined N-hydroxylation is an essential metabolic step for mutagenic activation of Trp-P-2.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D006168:Guinea Pigs; D006900:Hydroxylation; D007211:Indoles / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009153:Mutagens; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D002243:Carbolines; D007211:Indoles; D009153:Mutagens; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases